This proposal describes our intent to prepare chemical libraries based on important medicinally or natural product inspired scaffolds. We have created a small molecule screening platform to support the University of Utah's commitment to discovery based research activities. We believe that engaging the creativity of individuals within the synthetic community will lead to increased diversity with respect to compound architecture and function. Further this model is supported by individuals with a vested interest in the biological properties of their core architectures, the preparation of which has been inspired by the development of new methodologies. From both internal screening activities and known natural product activities, we have identified several important core structures that are poorly represented in the national screening infrastructure. These architectures are broadly identified as 1) diarylmethines; 2) 2-aminoimidazoles/cyclic guanidines and 3) dimeric indoles. Under the umbrella of these structural classes we have proposed the preparation of 14 chemical libraries to be submitted for screening at the MPLCN. PUBLIC HEALTH RELEVANCE: The proposed research has direct relevance to the mission of the MPLCN. Small molecule libraries will be prepared by the implementation of previously developed chemical methodologies from our individual laboratories. We are committed to delivering -2,500 compounds that will contribute to the fundamental chemical diversity represented in the MLPCN.